Finding what makes biofilms hard to defeat in lung infections

By Rajendrani Mukhopadhyay

Cystic fibrosis patients often combat lung infections. At the late stage of the infections, a bacterium called Pseudomonas aeruginosa becomes the persistent menace, forming a structure known as a biofilm. Bacterial biofilms are stubborn, tough structures that resist antibiotics and other means of removal. These structures also afflict AIDS and burn patients.

In a paper recently published in Molecular & Cellular Proteomics, researchers have examined the entire protein content of P. aeruginosa biofilms. Their aim is to identify the molecular pathways that are critical to biofilm formation and maintenance, processes that are not well understood.

Cezar Khursigara at the University of Guelph in Canada, who spearheaded the work, says that he and one of his postdoctoral fellows, Amber Park, “wanted to examine the proteome dynamics of P. aeruginosa cells as they transitioned from a planktonic, free-living state to a biofilm lifestyle. This transition is thought to be similar to the one P. aeruginosa makes in the lungs of patients with (cystic fibrosis), when pulmonary infections eventually move from an acute to chronic phase.”

The investigators compared the different protein expressions over time in P. aeruginosa cells as they developed through the two different lifestyles. They discovered that there were significant shifts in protein expression as the bacteria switched from the planktonic state to the biofilm state. In particular, they saw differences in expression of proteins involved in iron acquisition and a downregulation of key antimicrobial targets.

“Most surprisingly, however, was the dramatic increase in cellular adhesins that were identified only in the later time points and were completely absent in the earlier planktonic samples,” says Khursigara. “We feel these may play a role in shaping biofilm architecture and, as a result, may contribute to the resilience of these communities.”

The investigators now are working on P. aeruginosa isolated from patients and developing experimental conditions that better mimic those in the lung. They are also plunging deeper into the pathways they have identified to see if they can pinpoint particular proteins that may be suitable as drug targets. Khursigara notes, “With the number of proteins identified, we will be busy for a while.”